Human cytomegalovirus (CMV) has a particularly narrow host range. In cell cultures it replicates productively only in human fibroblasts. All other cell types are nonpermissive, supporting only an abortive infection. The causes of abortive infection are unknown, but at least two different mechanisms can be postulated: the absence of some essential cellular gene product(s) in nonpermissive cells, or the presence of inhibitory product(s). We are evaluating these alternatives using hybrid cells derived from one permissive (WI-38 cells) and one nonpermissive (bovine embryonic fibroblasts) parental cell type, and also using chimeric cells derived by Sendai-induced fusion of cytoplasts and karyoplasts obtained by enucleating parental cell types with cytochalasin B. Permissive x nonperissive hybrids and chimeras will be separated from parental cells by a technique of specific immunoadsorption which capitalizes on the dual population of species specific cell surface antigens carried by the newly created hybrids and chimeras. The separated hybrids or chimeras will be exposed to CMV and examined for the occurrence and time course of the following: (1) viral antigen synthesis as judged by complement fixation techniques, (2) viral DNA synthesis as judged by density gradient centrifugation, (3) viral morphogenesis as judged by electron microsocopy, and (4) production of infectious progeny as judged by plaque assays.